25 - Diuretics

Question 1

What are all the segments of the nephron that you need to be familiar with?

Answer 1

• Glomerulus
• Proximal convoluted tubule (PCT)
• Proximal tubule, straight segment
• Thin descending limb of Henle’s loop
• Thick ascending limb of Henle’s loop
• Distal convoluted tubule (DCT)
• Cortical collecting tubule (CCT)
• Medullary collecting duct

Question 2

Describe the glomerulus

Answer 2

• Function: formation of glomerulus filtrate
• Extremely high water permeability
• No primary transporters or drug targets here
• No diuretics act here

Question 3

Describe the proximal convoluted tubule (PCT)

Answer 3

• Function: reabsorption of 65% of filtered electrolytes (Na, K, Ca, Mg), 85% of NaHCO3, nearly 100% of glucose and amino acids, isosmotic reabsorption of water
• Very high water permeability
• Primary transporters and drug targets: Na+/H+ exchanger (NHE3), carbonic anhydrase
• Diuretic that works here: carbonic anhydrase inhibitors

Question 4

Describe the proximal tubule, straight segment

Answer 4

• Function: secretion and reabsorption of organic acids and bases, including uric acid and most diuretics
• Very high water permeability
• Primary transporter: Acid (uric acid) and base transporters
• No drugs target here

Question 5

Describe the thin descending limb of the loop of Henle

Answer 5

• Function: passive reabsorption of water
• High water permeability
• Primary transporter: aquaporins
• No drugs target here

Question 6

Describe the thick ascending limb of the loop of Henle

Answer 6

• Function: active reabsorption of 15-25% of filtered Na, K, Cl and secondary reabsorption of Ca and Mg
• Very low water permeability
• Primary transporter/drug target: Na/K/2Cl (NKCC2)
• Diuretic which targets here: NKCC inhibitors (loop diuretics)

Question 7

Describe the distal convoluted tubule (DCT)

Answer 7

• Function: active reabsorption of 4-8% of filtered Na+ and Cl-, Ca reabsorption (under parathyroid hormone control)
• Very low water permeability
• Primary transporter/drug target: Na/Cl (NCC)
• Diuretic which targets here: thiazides

Question 8

Describe the cortical collecting tubule (CCT)

Answer 8

• Function: Na+ reabsorption (2-5%) coupled to K+ and H+ secretion
• Variable water permeability
• Primary transporter/drug target: Na channels (ENaC), K chanels, H transporter, aquaporins
• Diuretic which targets here: K+ sparing diuretics

Question 9

Describe the medullary collecting duct

Answer 9

• Function: water reabsorption under vasopressin contol
• Variable water permeability
• Primary transporter/drug target: aquaporins
• Diuretic which targets here: vasopressin antagonist